We lack reliable methods to continuously assess localized, resting-state muscle activity that are comparable across individuals. Near-infrared spectroscopy (NIRS) provides a low-cost, non-invasive means to assess localized, resting-state muscle oxygen metabolism during venous or arterial occlusions (VO2VO and VO2AO, respectively). However, this technique is not suitable for continuous monitoring, and its utility is limited to those who can tolerate occlusions. Combining NIRS with diffuse correlated spectroscopy (DCS) enables continuous measurement of an index of muscle oxygen metabolism (VO2i). Despite the lack of previous validation, VO2i is employed as a measure of oxygen metabolism in the muscle. Here we characterized measurement repeatability and compared VO2i with VO2VO and VO2AO in the medial gastrocnemius (MG) in 9 healthy adults. Intra-participant repeatability of VO2i, VO2VO, and VO2AO were excellent. VO2i was not significantly correlated with VO2AO (p = 0.15) nor VO2VO (p = 0.55). This lack of correlation suggests that the variability in the calibration coefficient between VO2i and VO2AO/VO2VO in the MG is substantial across participants. Thus, it is preferable to calibrate VO2i prior to every monitoring session. Important future work is needed to compare VO2i against gold standard modalities such as positron emission tomography or magnetic resonance imaging.

The objective of this pilot study was to characterize relationships between skeletal muscle energy metabolism and body composition in healthy adults with varied amounts and distribution of adipose tissue. In vivo muscle energetics were quantified using dynamic 31P magnetic resonance spectroscopy with knee extension exercise standardized to subject lean body mass. Spearman correlation analysis examined relationships between muscle metabolism indices and measures of adiposity including body mass index (BMI), total body fat, and quadriceps intermuscular adipose tissue (IMAT). Post-hoc partial correlations were examined controlling for additional body composition measures. Kruskal-Wallis tests with Dunn-Sidak post-hoc comparisons evaluated group differences in energy metabolism based on body composition profiles (i.e. lean, normal-weight obese, and overweight-obese) and IMAT tertiles. BMI negatively correlated with end-exercise muscle pH after correcting for IMAT and total body fat (r=-0.46, p=.034). Total adiposity negatively correlated with maximum oxidative capacity after correcting for IMAT (r=-0.54, p=.013). IMAT positively correlated with muscle proton buffering capacity after correcting for total body fat (r=0.53, p=.023). Body composition groups showed differences in end-exercise fall in [PCr] with normalized workload (p=.036; post-hoc: overweight-obese < lean, p=.029) and maximum oxidative capacity (p=.021; post-hoc: normal-weight obese < lean, p=.016). IMAT tertiles showed differences in end-exercise fall in [PCr] with normalized workload (p=.035; post-hoc: 3rd < 1st, p=.047). Taken together, these results support increased adiposity is associated with reduced muscle energetic efficiency with more reliance on glycolysis, and when accompanied with reduced lean mass, is associated with reduced maximum oxidative capacity.

Objectives Obesity, body composition, and mitochondrial dysfunction play important roles in the development of metabolic diseases, but it is unknown if increased visceral fat (VF) specifically alters mitochondrial bioenergetic capacity. We determined whether in vivo and ex vivo bioenergetic indexes are associated with total body composition, visceral fat (VF), and body composition subtypes. Methods This pilot study included 34 healthy adults (56% female, median age 27.9 y). Body composition and fat distribution were assessed by dual energy x-ray absorptiometry. Subjects were categorized as lean (BMI < 25 kg/m2, n = 14), normal weight obese (NWO, BMI < 25 kg/m2 and >30% body fat in women or >23% body fat in men, n = 8), or overweight/obese (O/O, BMI > 25 kg/m2, n = 12). Ex vivo mitochondrial function was assessed using a Seahorse extracellular flux analyzer in peripheral blood mononuclear cells (PBMC) and isolated monocytes. In a subset (n = 21), maximum in vivo ATP synthesis was assessed in the quadriceps using 31P-Magnetic resonance spectroscopy based on the phosphocreatine recovery time constant (τPCr) following a standardized leg exercise. Statistical analyses included Spearman correlations and Kruskal-Wallis tests. Results In monocytes, but not PBMCs, % spare respiratory capacity was inversely associated with % body fat (r = −0.42, P = 0.02) and positively associated with lean body mass (r = 0.36, P = 0.04) but was not significantly associated with VF. Skeletal muscle τPCr was positively associated with % body fat (r = 0.58, P < 0.01) and total body fat (r = 0.53, P = 0.02) but not VF. Subjects with NWO had the highest τPCr (P = 0.01) and lowest % spare respiratory capacity (P = 0.09 and 0.03 in monocytes and PBMCs, respectively) compared to lean or O/O subjects. Conclusions Total body fat, but not VF, was associated with impaired mitochondrial function as shown by increased post-exercise recovery time in skeletal muscle and decreased response to energy demands in circulating cells. Adults with NWO had worse bioenergetic capacity than O/O or lean adults. These data provide insight on the relationships between human body composition and mitochondrial energy metabolism, which plays a role in metabolic disease progression. Funding Sources National Institutes of Health, Georgia Clinical and Translational Science Alliance.